Clinical pharmacological studies will be carried out to improve chemotherapy of cancer by (1) identifying the biochemical pharmacological and pharmacokinetic parameters of response to chemotherapeutic agents in patients with leukemia and solid tumors, and (2) development of new drugs and drug combinations. Metabolism of fluorinated pyrimidines in tumor of patients with colon carcinoma and of ara-C in leukemic blast cells will be correlated with response to those agents and specific DNA damage in leukemic cells with response to DNA interactive agents. Solid tumors from melanoma, sarcoma, colon carcinoma and other tumors will be disaggregated by newly developed enzymatic methods and used to study the multiplicity of parameters of response to chemotherapy. Soft agar cloning will be used to study drug sensitivity and DNA and RNA profiles measured cytofluorographically will be used to study drug response. Studies on lymphomas will include isolation of subsets for differential studies of drug metabolism and studies of cytoplasmic and nuclear receptors as parameters of response to glucocorticoids. Studies on new drugs will include phase I studies of new agents integrated with pharmacokinetic and drug metabolism studies using GC/MS techniques. Metabolite antimetabolite combinations developed on the basis of preclinical studies as part of this program will be developed and tested clinically. Pharmacokinetic studies will be carried out of regional perfusion and to correlate adriamycin and ara-C pharmacokinetics with response. A biomathematics unit is an integral part of the program to develop mathematical, statistical and computer techniques to solve the analytical problems arising in the course of the program.